There is a growing recognition of the need for effective therapeutic strategies to treat breast cancer patients that are less toxic than chemotherapy. Since the discovery of the hormonal dependency of many breast cancers, endocrine therapy has been extensively investigated.
Fulvestrant is a pure antiestrogen that represent a significant breakthrough in the treatment of breast cancer. Despite its pure antagonist activity, studies on ovariectomized rats have confirmed that fulvestrant, in contrast to Tamoxifen which acts like estrogen to reduce periosteal bone formation, does not alter estrogen-like or antiestrogenic effects. Fulvestrant also has some distinct advantages on target organs other than breast tissue.
Fulvestrant is a steroidal pure antiestrogen with a chemical structure similar to estradiol. Studies of estrogen receptor (ER) function have demonstrated that estradiol binding to the ER initiate a sequence of events. Fulvestrant antagonizes estrogen action by occupying the ER and preventing estrogen-stimulated gene activation, thus interfering with the estrogen related processes essential for cell-cycle completion.
Fulvestrant, 7-alpha-[9-(4,4,5,5,5pentafluoropentylsulphinyl)nonyl]-estra-1,3,5(10)-triene-3,17β-diol, has the following formula:

WO Patent application No. 02/32922 describes a process for preparing an intermediate compound useful for preparing, e.g. fulvestrant, which process comprises aromatization of a compound, and thereafter if necessary or desired, carrying out one or more of the following steps: (i) removing any hydroxy protecting group; (ii) converting a precursor group to a different such group.
EP Patent No. 0138504 relates to certain 7α-substituted derivatives of oestradiol and related steroids which possess antioestrogenic activity. U.S. Pat. No. 4,659,516, EP Patent No. 0138504 and Bowler, Steroids 1989, 54, 71 describe a process for making steroids such as fulvestrant, by which 1,6-conjugate addition of an alkyl group to an estra-4,6-diene-3-one gave a ratio of 7α- to 7β-epimer of 1.2:1 (isolated). In WO 02/92322 it is stated that the ratio of epimers obtained using this process on an industrial scale is 1.9:1.
U.S. Pat. No. 6,288,051 describes 7α-(5-methylaminopentyl)-estratrienes.
There remains a need in the art for improved methods of preparing fulvestrant and other 7α-alkylated 19-norsteroids.